The Effect of Acetylsalicylic Acid (ASA) on the Mechanical Properties of Breast Cancer Epithelial Cells

Background: In most communities, the risk of developing breast cancer is increasing. By affecting the cyclooxygenase 1 and 2 (COX-1 and COX-2) enzymes and actin filaments, acetylsalicylic acid (Aspirin) has been shown to reduce the risk of breast cancer and prevent cell migration in both laboratory and clinical studies. Methods: The purpose of this study is to determine the mechanical properties of normal and cancerous breast tissue cells, as well as the short-term effect of aspirin on cancer cells. To this end, the mechanical properties and deformation of three cell types were investigated: healthy MCF-10 breast cells, MCF-7 breast cancer cells, and MCF-7 breast cancer cells treated with a 5 µM aspirin solution. Atomic Force Microscopy (AFM) was used to determine the mechanical properties of the cells. Cell deformation was analyzed in all groups, and Young's modulus was calculated using the Hertz model. Result: According to the obtained data, cancer cells deformed at a rate half that of healthy cells. Nonetheless, when aspirin was used, cancer cells deformed similarly to healthy cells. Additionally, healthy cells' Young's modulus was calculated to be approximately three times that of cancer cells, which was placed closer to that of healthy cells by adding aspirin to Young's modulus. Conclusion: Cell strength appears to have increased due to aspirin's intervention on actin filaments and cytoskeletons, and the mechanical properties of breast cancer cells have become more similar to those of normal cells. The likelihood of cell migration and metastasis decreases as cell strength increases.

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Biomechanical and Biophysical Properties of Breast Cancer Cells Under Varying Glycemic Regimens

Breast Cancer Basic and Clinical Research ◽

10.1177/1178223420972362 ◽

2020 ◽

Vol 14 ◽

pp. 117822342097236

Author(s):

Diganta Dutta ◽

Xavier-Lewis Palmer ◽

Jose Ortega-Rodas ◽

Vasundhara Balraj ◽

Indrani Ghosh Dastider ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Young’S Modulus ◽

High Glucose ◽

Breast Cancer Cells ◽

Mammary Epithelial Cells ◽

Young's Modulus ◽

Malignant Cells ◽

Biophysical Properties ◽

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Diabetes accelerates cancer cell proliferation and metastasis, particularly for cancers of the pancreas, liver, breast, colon, and skin. While pathways linking the 2 disease conditions have been explored extensively, there is a lack of information on whether there could be cytoarchitectural changes induced by glucose which predispose cancer cells to aggressive phenotypes. It was thus hypothesized that exposure to diabetes/high glucose alters the biomechanical and biophysical properties of cancer cells more than the normal cells, which aids in advancing the cancer. For this study, atomic force microscopy indentation was used through microscale probing of multiple human breast cancer cells (MCF-7, MDA-MB-231), and human normal mammary epithelial cells (MCF-10A), under different levels of glycemic stress. These were used to study both benign and malignant breast tissue behaviors. Benign cells (MCF-10A) recorded higher Young’s modulus values than malignant cells (MCF-7 and MDA-231) under normoglycemic conditions, which agrees with the current literature. Moreover, exposure to high glucose (for 48 hours) decreased Young’s modulus in both benign and malignant cells, to the effect that the cancer cells showed a complete loss in elasticity with high glucose. This provides a possible insight into a link between glycemic stress and cytoskeletal strength. This work suggests that reducing glycemic stress in cancer patients and those at risk can prove beneficial in restoring normal cytoskeletal structure.

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On-chip cell migration assay for quantifying the effect of ethanol on MCF-7 human breast cancer cells

Microfluidics and Nanofluidics ◽

10.1007/s10404-011-0766-9 ◽

2011 ◽

Vol 10 (6) ◽

pp. 1333-1341 ◽

Cited By ~ 24

Author(s):

Xiaowen Huang ◽

Li Li ◽

Qin Tu ◽

Jianchun Wang ◽

Wenming Liu ◽

...

Keyword(s):

Breast Cancer ◽

Cell Migration ◽

Cancer Cells ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Human Breast Cancer Cells ◽

Human Breast ◽

Migration Assay ◽

On Chip ◽

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Proton pump inhibitors enhance chemosensitivity, promote apoptosis, and suppress migration of breast cancer cells

Acta Pharmaceutica ◽

10.2478/acph-2020-0020 ◽

2020 ◽

Vol 70 (2) ◽

pp. 179-190 ◽

Cited By ~ 3

Author(s):

Worood G. Ihraiz ◽

Mamoun Ahram ◽

Sanaa K. Bardaweel

Keyword(s):

Breast Cancer ◽

Cell Migration ◽

Synergistic Effect ◽

Cancer Cells ◽

Cell Lines ◽

Proton Pump ◽

Breast Cancer Cells ◽

Combined Treatment ◽

Combined Effects ◽

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AbstractBreast cancer is the most common cancer and is the leading cause of cancer deaths among women worldwide. Despite the availability of numerous therapeutics for breast cancer management, cytotoxicity and emergence of drug resistance are major challenges that limit their benefits. The acidic microenvironment surrounding tumor cells is a common feature inducing cancer cell invasiveness and chemoresistance. Proton pump inhibitors (PPIs) are one of the most commonly prescribed drugs for the treatment of acid-related conditions. PPIs have been reported to exhibit antitumorigenic effects in many cancer types. In this study, the anti-proliferative and anti-migratory effects of PPIs in three breast cancer cell lines; MCF-7, T47D, and MDA-MB-231 cells, have been investigated. In addition, the combined effects of PPIs with anticancer drugs, as well as the mechanism of PPI-mediated anti-proliferative activity were evaluated. The anti-proliferative and combined effects of PPIs were evaluated by MTT assay. Cell migration was assessed using the wound-healing assay. The mechanism of cell death was assessed using annexin V-FITC/propidium iodide staining flow cytometry method. Our results indicated that PPIs treatment significantly inhibited the growth of breast cancer cells in a dose-dependent manner. The antiproliferative activity of PPIs was significantly induced by apoptosis in all tested cell lines. The combined treatment of PPIs with doxorubicin resulted in a synergistic effect in all cell lines, whereas the combined treatment with raloxifene exhibited synergistic effect in T47D cells only and additive effects in MDA-MB-231 and MCF-7 cells. In addition, PPIs treatment significantly reduced cell migration in MDA-MB-231 cells. In conclusion, the addition of PPIs to the treatment regimen of breast cancer appears to be a promising strategy to potentiate the efficacy of chemotherapy and may suppress cancer metastasis.

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microRNA-548m suppresses cell migration and invasion by targeting aryl hydrocarbon receptor in breast cancer cells

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics ◽

10.3727/096504020x16037933185170 ◽

2020 ◽

Author(s):

WM Farhan Syafiq B WM Nor ◽

Ivy Chung ◽

Nur Akmarina B M Said

Keyword(s):

Breast Cancer ◽

Cell Migration ◽

Aryl Hydrocarbon Receptor ◽

Cancer Cells ◽

Cell Lines ◽

Breast Cancer Cells ◽

Migration And Invasion ◽

Cell Migration And Invasion ◽

Aryl Hydrocarbon ◽

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Breast cancer is the most commonly diagnosed cancer among women and one of the leading causes of cancer mortality worldwide, in which the most severe form happens when it metastasizes to other regions of the body. Metastasis is responsible for most treatment failures in advanced breast cancer. Epithelial-mesenchymal transition (EMT) plays a significant role in promoting metastatic processes in breast cancer. MicroRNAs (miRNAs) are highly conserved endogenous short non-coding RNAs that play a role in regulating a broad range of biological processes, including cancer initiation and development, by functioning as tumor promoters or tumor suppressors. Expression of miR-548m has been found in various types of cancers, but the biological function and molecular mechanisms of miR-548m in cancers have not been fully studied. Here, we demonstrated the role of miR-548m in modulating EMT in the breast cancer cell lines MDA-MB-231 and MCF-7. Expression data for primary breast cancer obtained from NCBI GEO datasets showed that miR-548m expression was downregulated in breast cancer patients compared with healthy group. We hypothesize that miR-548m acts as a tumor suppressor in breast cancer. Overexpression of miR-548m in both cell lines increased E-cadherin expression and decreased the EMT-associated transcription factors SNAI1, SNAI2, ZEB1 and ZEB2, as well as MMP9 expression. Consequently, migration and invasion capabilities of both MDA-MB-231 and MCF-7 cells were significantly inhibited in miR-548m-overexpressing cells. Analysis of 1059 putative target genes of miR-548m revealed common pathways involving both tight junction and the mTOR signaling pathway, which has potential impacts on cell migration and invasion. Furthermore, this study identified aryl hydrocarbon receptor (AHR) as a direct target of miR-548m in breast cancer cells. Taken together, our findings suggest a novel function of miR-548m in reversing the EMT of breast cancer by reducing their migratory and invasive potentials, at least in part via targeting AHR expression.

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Artemisinic acid exhibits antitumor activity in MCF-7 breast cancer cells through the inhibition of angiogenesis, VEGF, m-TOR and AKT signalling pathways

Bangladesh Journal of Pharmacology ◽

10.3329/bjp.v11i3.26512 ◽

2016 ◽

Vol 11 (3) ◽

pp. 691

Author(s):

Yan Cui ◽

Hui Ren ◽

Hao-Chang Li ◽

Quan-Shi Wang

Keyword(s):

Breast Cancer ◽

Cell Migration ◽

Antitumor Activity ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Tube Formation ◽

Signalling Pathways ◽

Artemisinic Acid ◽

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The aim of the present study was to evaluate the antitumor and anti-angiogenic effects of artemisinic acid in MCF-7 human breast cancer cells. Various cell signalling pathways (VEGF, m-TOR and AKT signalling pathways) and MTT assay were used. The in vivo antitumor activity of artemisinic acid was evaluated by means of tumor xenograft mouse model. Transwell cell migration assay was used to examine the chemotactic motility of the human umbilical vascular endothelial cells (HUVECs), while as endothelial cell capillary-like tube formation assay was used to evaluate the effect of artemisinic acid on the tube formation in HUVECs. We found that artemisinic acid considerably reduced both the volume and weight of concrete tumors and reduced angiogenesis in a xenograft mouse tumor model in vivo. Further, artemisinic acid suppressed the VEGF-induced cell migration and capillary-like tube formation of HUVECs in a dose-dependent manner. Artemisinic acid was found to suppress the VEGF-induced phosphorylation of VEGFR2 and also the activity of AKT and m-TOR.Video Clip:<a href="https://youtube.com/v/w7jZqcDvMTc">Western blot assay:</a> 4 min 33 sec

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Increased expression of both insulin receptor substrates 1 and 2 confers increased sensitivity to IGF-1 stimulated cell migration

Endocrine Related Cancer ◽

10.1677/erc-08-0216 ◽

2009 ◽

Vol 16 (2) ◽

pp. 635-647 ◽

Cited By ~ 14

Author(s):

Gail E de Blaquière ◽

Felicity E B May ◽

Bruce R Westley

Keyword(s):

Breast Cancer ◽

Cell Migration ◽

Insulin Receptor ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Type I ◽

Migratory Response ◽

Type I Igf Receptor ◽

Igf Receptor ◽

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Insulin-like growth factors (IGFs) are thought to promote tumour progression and metastasis in part by stimulating cell migration. Insulin receptor substrate-1 (IRS-1) and IRS-2 are multisite docking proteins positioned immediately downstream from the type I IGF and insulin receptors. IRS-2 but not IRS-1 has been reported to be involved in the migratory response of breast cancer cells to IGFs. The purpose of this investigation was to determine if IRS-1 is involved in, and to assess the contributions of IRS-1 and IRS-2 to, the migratory response of breast cancer cells to IGFs. The expression of IRS-1 and IRS-2 varied considerably between ten breast cancer cell lines. Oestrogen increases expression of the type I IGF receptor, IRS-1 and IRS-2 in MCF-7 and ZR-75 cells. Oestrogens may control the sensitivity of breast cancer cells to IGFs by regulating the expression of components of the IGF signal transduction pathway. The migratory response to a range of IGF-1 concentrations was measured in MCF-7 and MDA-MB-231 breast cancer cells in which IRS-1 and IRS-2 levels were modulated using a doxycycline-inducible expression system. Induction of both IRS-1 and IRS-2 expression increased the sensitivity of the migratory response to IGF-1 but did not increase the magnitude of the response stimulated at higher concentrations of IGF-1. Knockdown of IRS-1, IRS-2 and the type I IGF receptor in MCF-7 and MDA-MB-2231 cells decreased sensitivity to IGF-1. We conclude that both IRS-1 and IRS-2 control the migratory response of breast cancer cells to IGF-1 and may, therefore, be key molecules in determining breast cancer spread.

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Deferoxamine Enhanced Mitochondrial Iron Accumulation and Promoted Cell Migration in Triple-Negative MDA-MB-231 Breast Cancer Cells Via a ROS-Dependent Mechanism

International Journal of Molecular Sciences ◽

10.3390/ijms20194952 ◽

2019 ◽

Vol 20 (19) ◽

pp. 4952 ◽

Cited By ~ 2

Author(s):

Chunli Chen ◽

Shicheng Wang ◽

Ping Liu

Keyword(s):

Breast Cancer ◽

Cell Migration ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Triple Negative ◽

Iron Concentration ◽

Cell Types ◽

Iron Deficient ◽

Mitochondrial Iron ◽

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In our previous study, Deferoxamine (DFO) increased the iron concentration by upregulating the expression levels of TfR1 and DMT1 and exacerbated the migration of triple-negative breast cancer cells. However, the mechanisms of iron distribution and utilization in triple-negative breast cancer cells with a DFO-induced iron deficiency are still unclear. In this study, triple-negative MDA-MB-231 and estrogen receptor (ER)-positive MCF-7 breast cancer cells were used to investigate the mechanisms of iron distribution and utilization with a DFO-induced iron deficiency. We found that the mitochondrial iron concentration was elevated in MDA-MB-231 cells, while it was decreased in MCF-7 cells after DFO treatment. The cellular and mitochondrial reactive oxygen species (ROS) levels increased in both breast cancer cell types under DFO-induced iron-deficient conditions. However, the increased ROS levels had different effects on the different breast cancer cell types: Cell viability was inhibited and apoptosis was enhanced in MCF-7 cells, but cell viability was maintained and cell migration was promoted in MDA-MB-231 cells through the ROS/NF-κB and ROS/TGF-β signaling pathways. Collectively, this study suggests that under DFO-induced iron-deficient conditions, the increased mitochondrial iron levels in triple-negative MDA-MB-231 breast cancer cells would generate large amounts of ROS to activate the NF-κB and TGF-β signaling pathways to promote cell migration.

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